Natriuretic peptide determinations in critical care medicine: part of routine clinical practice or research test only?

Measurement of N-terminal pro-B-type natriuretic peptide has been shown a good rule-out test for cardiac dysfunction in patients in the intensive care unit. The peptide measurement should not be used as a replacement for other forms of monitoring, and performs best as a diagnostic test when interpreted together with other clinical findings and investigations. At a cutoff value similar to that found in other clinical studies in acute decompensated heart failure, measurement of N-terminal pro-B-type natriuretic peptide offers an additional tool for diagnostic assessment of patients presenting to the intensive care physician

Implementation of the European Society of Cardiology 0/3-hour accelerated diagnostic protocol, using high sensitive troponin T: a clinical practice evaluation of safety and effectiveness involving 3003 patients with suspected acute coronary syndrome.

BackgroundThere have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn).ObjectiveTo analyse the safety and effectiveness of early emergency department (ED) discharge following implementation of the European Society of Cardiology (ESC) 0/3-hour ADP for suspected acute coronary syndromes (ACS).MethodWe prospectively studied 2 cohorts of consecutive suspected ACS presentations to ED before (n=1642) and after (n=1376, 2 centres) implementation of the ESC 0/3-hour ADP incorporating limit of detection rule out. Safety was defined by MACE (major adverse cardiac events) inclusive of type 1 myocardial infarction (MI) in patients discharged from ED, and clinical effectiveness by percentage ED discharge. Continuous variables and categorical data were evaluated by independent t-test and χ2 test, respectively. Time-to-event data were analysed as survival data and converted to Kaplan-Meier curves for interpretation.ResultsIn the preimplementation period, there was a higher prevalence of MI. Discharge from ED increased by >100% (from 27.1% to 56.5% of the cohort) with no safety signal (MACE rate 4/444 (0.9%) vs 4/769 (0.52%), p=0.430 for the 2011 and 2018 cohort, respectively). This correlated with a marked reduction in length of stay overall but a more modest reduction for those discharged from ED (6 hours 10 min vs 5 hours 25 min, pConclusionsImplementation of an ADP with hs-cTn is safe and effective for early rule-out and discharge of suspected ACS but require considerable resources and education to optimise maximal patient flow

Cardiac troponins: from myocardial infarction to chronic disease.

Elucidation of the physiologically distinct subunits of troponin in 1973 greatly facilitated our understanding of cardiac contraction. Although troponins are expressed in both skeletal and cardiac muscle, there are isoforms of troponin I/T expressed selectively in the heart. By exploiting cardiac-restricted epitopes within these proteins, one of the most successful diagnostic tests to-date has been developed: cardiac troponin (cTn) assays. For the past decade, cTn has been regarded as the gold-standard marker for acute myocardial necrosis: the pathological hallmark of acute myocardial infarction (AMI). Whilst cTn is the cornerstone for ruling-out AMI in patients presenting with a suspected acute coronary syndrome (ACS), elevated cTn is frequently observed in those without clinical signs indicative of AMI, often reflecting myocardial injury of 'unknown origin'. cTn is commonly elevated in acute non-ACS conditions, as well as in chronic diseases. It is unclear why these elevations occur; yet they cannot be ignored as cTn levels in chronically unwell patients are directly correlated to prognosis. Paradoxically, improvements in assay sensitivity have meant more differential diagnoses have to be considered due to decreased specificity, since cTn is now more easily detected in these non-ACS conditions. It is important to be aware cTn is highly specific for myocardial injury, which could be attributable to a myriad of underlying causes, emphasising the notion that cTn is an organ-specific, not disease-specific biomarker. Furthermore, the ability to detect increased cTn using high-sensitivity assays following extreme exercise is disconcerting. It has been suggested troponin release can occur without cardiomyocyte necrosis, contradicting conventional dogma, emphasising a need to understand the mechanisms of such release. This review discusses basic troponin biology, the physiology behind its detection in serum, its use in the diagnosis of AMI, and some key concepts and experimental evidence as to why cTn can be elevated in chronic diseases

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

Background: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. Methods: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. Results: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was ≤5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between −5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3mmol/L), icteric blood (bilirubin concentrations up to 582μmol/L), haemolytic blood (haemoglobin concentrations up to 62mg/L), biotin (up to 10mg/L), rheumatoid factor (up to 42IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165μL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. Conclusions: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting. Clin Chem Lab Med 2006;44:1269-7

Addressing robustness in time-critical, distributed, task allocation algorithms.

The aim of this work is to produce and test a robustness module (ROB-M) that can be generally applied to distributed, multi-agent task allocation algorithms, as robust versions of these are scarce and not well-documented in the literature. ROB-M is developed using the Performance Impact (PI) algorithm, as this has previously shown good results in deterministic trials. Different candidate versions of the module are thus bolted on to the PI algorithm and tested using two different task allocation problems under simulated uncertain conditions, and results are compared with baseline PI. It is shown that the baseline does not handle uncertainty well; the task-allocation success rate tends to decrease linearly as degree of uncertainty increases. However, when PI is run with one of the candidate robustness modules, the failure rate becomes very low for both problems, even under high simulated uncertainty, and so its architecture is adopted for ROB-M and also applied to MIT’s baseline Consensus Based Bundle Algorithm (CBBA) to demonstrate its flexibility. Strong evidence is provided to show that ROB-M can work effectively with CBBA to improve performance under simulated uncertain conditions, as long as the deterministic versions of the problems can be solved with baseline CBBA. Furthermore, the use of ROB-M does not appear to increase mean task completion time in either algorithm, and only 100 Monte Carlo samples are required compared to 10,000 in MIT’s robust version of the CBBA algorithm. PI with ROB-M is also tested directly against MIT’s robust algorithm and demonstrates clear superiority in terms of mean numbers of solved tasks.N/

Jography: Exploring meanings, experiences and spatialities of recreational road-running

Jogging is a relatively under-researched mobile practice with much existing literature focusing on ‘serious’ and competitive running. In this paper, we provide an account of some of the movements, meanings and experiences that together help produce the practice of jogging in the south-western English city of Plymouth. Drawing upon participant diaries and interviews, we uncover rich detail about how joggers ascribe not one but a number of meanings to their practice. Some of these are positive, some are negative; some complement each other and some compete with each other. We also consider how the experiences of joggers can be shaped by their ongoing need to develop tactics capable of enabling them to negotiate space with non-joggers. This is in some contrast to more competitive running that occurs in the separated space of an athletics track. Our sense is that better awareness of the meanings and experiences of jogging will be of value if the advertised health and sustainability benefits of the practice are to be more effectively encouraged and promoted

Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.

Background: Sepsis and bacterial meningitis are major causes of mortality and morbidity in neonates and infants. Meropenem, a broad-spectrum antibiotic, is not licensed for use in neonates and infants below 3 months of age and sufficient information on its plasma and CSF disposition and dosing in neonates and infants is lacking. Objectives: To determine plasma and CSF pharmacokinetics of meropenem in neonates and young infants and the link between pharmacokinetics and clinical outcomes in babies with late-onset sepsis (LOS). Methods: Data were collected in two recently conducted studies, i.e. NeoMero-1 (neonatal LOS) and NeoMero-2 (neonatal meningitis). Optimally timed plasma samples (n = 401) from 167 patients and opportunistic CSF samples (n = 78) from 56 patients were analysed. Results: A one-compartment model with allometric scaling and fixed maturation gave adequate fit to both plasma and CSF data; the CL and volume (standardized to 70 kg) were 16.7 (95% CI 14.7, 18.9) L/h and 38.6 (95% CI 34.9, 43.4) L, respectively. CSF penetration was low (8%), but rose with increasing CSF protein, with 40% penetration predicted at a protein concentration of 6 g/L. Increased infusion time improved plasma target attainment, but lowered CSF concentrations. For 24 patients with culture-proven Gram-negative LOS, pharmacodynamic target attainment was similar regardless of the test-of-cure visit outcome. Conclusions: Simulations showed that longer infusions increase plasma PTA but decrease CSF PTA. CSF penetration is worsened with long infusions so increasing dose frequency to achieve therapeutic targets should be considered